Psychiatric diagnoses are often made from patterns of symptoms, behaviour, history and clinical observation. Those tools are important—but when a diagnosis is questionable, atypical, unusually severe, treatment-resistant or accompanied by cognitive or neurological changes, they should not necessarily be the end of the investigation.

A questionable psychiatric diagnosis should trigger a serious search for neurological, cognitive, metabolic and endocrine explanations.

This is not an argument that psychiatric illness is “not real,” nor that every person with depression, psychosis, bipolar disorder or another psychiatric condition needs an enormous battery of tests. It is an argument for diagnostic humility: before permanently attributing unexplained changes in behaviour, personality, cognition or perception to a psychiatric disorder, clinicians should ask whether the brain and the body’s underlying physiology have been adequately investigated.

Start with objective cognitive testing

A detailed neuropsychological or neurological cognitive assessment can provide information that a conventional psychiatric interview may miss.

Memory, attention, processing speed, language, executive functioning, visuospatial abilities and working memory can be measured systematically. Patterns of impairment may point toward neurological disease, acquired brain injury, neurodegenerative processes or other conditions that can present with apparently psychiatric symptoms.

This is particularly important when someone reports a significant change from their previous cognitive functioning. The question should not simply be, “Does this person meet the criteria for a psychiatric disorder?” It should also be, “What has happened to this person’s brain function?”

Modern neuropsychiatric assessment explicitly recognises the importance of cognitive, neurological and laboratory information in understanding difficult presentations. 

MRI should not be dismissed when the presentation is unusual

When there is a credible possibility of neurological disease or brain injury, high-quality brain MRI deserves consideration.

MRI is generally more informative than CT for many structural brain abnormalities and provides better visualisation of grey and white matter and certain deeper brain structures. Neuropsychiatric references identify circumstances such as new-onset psychosis, cognitive decline, new personality change, seizures, traumatic brain injury and treatment-refractory presentations as situations in which structural imaging may warrant consideration.

The point is not that an MRI will automatically reveal the cause. It often will not. Nor should the phrase “high-resolution MRI” become a promise that subtle psychiatric symptoms can be explained by a scan.

The point is simpler: if neurological damage or disease is genuinely in the differential diagnosis, it should be investigated rather than assumed away. NICE material on first-episode psychosis likewise recognises neurological examination and targeted laboratory and EEG investigation, with MRI or CT considered when an organic cause is suspected.

EEG deserves consideration when electrical brain dysfunction is plausible

Some neurological disorders can produce behavioural, perceptual or cognitive symptoms that can be mistaken for psychiatric illness.

Seizure disorders are an obvious example. EEG is particularly relevant where there are episodes that are sudden, stereotyped, episodic or otherwise suggestive of abnormal electrical activity. Psychiatric assessment guidance notes that continuous or ambulatory EEG can sometimes be necessary to document abnormal activity when ordinary testing does not capture an event. 

That is why, where the clinical history makes intermittent electrical dysfunction plausible, a normal short routine EEG should not automatically end the neurological investigation.

In selected cases, prolonged ambulatory or video EEG, including a 48-hour study where clinically justified may provide substantially more opportunity to capture abnormalities than a brief recording.

But this distinction matters: a 48-hour EEG should be clinically indicated, not imposed indiscriminately on every psychiatric patient. Current psychiatric guidance generally describes EEG as an investigation to use when neurological history or examination raises the possibility of a seizure disorder or other neurological process. 

Endocrine and metabolic causes should be taken seriously

The brain does not operate independently of the rest of the body.

Thyroid dysfunction, metabolic abnormalities and other systemic illnesses can produce changes in mood, cognition, energy, sleep, behaviour and mental state. Consequently, laboratory investigation belongs in the differential diagnosis of unexplained psychiatric and cognitive presentations.

There is already recognition within psychiatric practice that physical and laboratory assessment is an important component of diagnosis and management. Standard investigations can include thyroid function and metabolic testing, with additional testing guided by the individual’s presentation. The principle should therefore be:

Do not diagnose the mind while ignoring the body.

Where symptoms suggest an endocrine disorder, the appropriate endocrine investigation should be pursued rather than assuming that psychiatric symptoms are necessarily primary.

This is not “psychiatry versus neurology”

The false choice is between saying that somebody has a psychiatric illness and saying that they have a neurological illness. Sometimes the answer is both. Sometimes neither initial diagnosis is correct.

A person can have a psychiatric disorder and a neurological disorder. Brain injury can coexist with depression. Epilepsy can coexist with anxiety. Endocrine disease can produce psychiatric symptoms. Medication, substances, sleep disorders and systemic illness can complicate an otherwise genuine psychiatric condition.

Neuropsychiatry exists precisely because the boundary between neurological and psychiatric presentations is not as clean as diagnostic labels can sometimes imply. The professional literature explicitly advocates an integrated approach rather than a rigid division between “psychiatric” and “neurological” disease.

The standard should be diagnostic confidence—not diagnostic convenience

The strongest case is not for testing everyone. It is for testing appropriately when the diagnosis does not adequately explain the person in front of you.

Red flags might include:

• a sudden or unusually late onset of psychiatric symptoms;
• substantial or unexplained cognitive decline;
• new personality or behavioural change;
• episodes suggesting seizures or altered consciousness;
• focal neurological symptoms or abnormal neurological findings;
• a history of significant head injury;
• an unusually atypical clinical presentation;
• rapid deterioration;
• unexpected treatment resistance; or
• a substantial discrepancy between the psychiatric diagnosis and the person’s observed cognitive or neurological functioning.

These are precisely the sorts of circumstances in which psychiatric literature recommends considering additional medical or neurological evaluation. 

A more rigorous standard

When a psychiatric diagnosis is questionable, the appropriate response should not be to simply repeat the same psychiatric assessment until the original diagnosis appears more convincing.

It should be to expand the differential diagnosis. That may mean comprehensive cognitive testing, neurological examination, appropriate blood and endocrine investigations, high-quality brain MRI, and, when the history warrants it prolonged EEG monitoring such as a 48-hour ambulatory study.

None of these tests is infallible. None should be treated as a magical machine capable of proving or disproving a psychiatric diagnosis. And indiscriminate testing can create false positives, unnecessary anxiety and inappropriate treatment.

But the opposite error can be far more consequential: mistaking an unexplained neurological, cognitive or physiological disorder for a purely psychiatric one and never looking for anything else.

A psychiatric label should be a clinical hypothesis supported by evidence—not a reason to stop investigating.

When the diagnosis is questionable, the brain deserves to be examined, cognition deserves to be measured, electrical activity deserves to be considered, and the body’s physiology deserves to be investigated.

Good psychiatry should not fear neurological investigation. It should demand it when the clinical picture warrants it.

This is a drug well known to us for terrible adverse reactions – severe restlessness and Akathisia, not to mention excessive expenditure on shopping.. Once again it is prescribed off- label to counteract the effects of hyperprolactinaemia caused by another, despite substantial physical health decline and metabolic issues. This drug should not be accepted as any substitute for essential pathophysiological referrals and tests when there is overwhelming evidence in terms of need. I have highlighted the very important point on appropriateness. I will also highlight applicable issues below

The use of adjunctive aripiprazole to treat antipsychotic-induced hyperprolactinaemia has become an increasingly accepted off-label strategy within psychiatric practice. Randomised trials and systematic reviews demonstrate that low-dose aripiprazole can reduce serum prolactin concentrations in many patients receiving prolactin-raising antipsychotics. Yet clinical efficacy alone does not determine whether prescribing is appropriate.

Where treatment is off-label, the patient remains prescribed a long-acting depot antipsychotic, and there is evidence of multiple endocrine or metabolic abnormalities, the clinician’s responsibilities extend well beyond correcting a biochemical abnormality. The decision engages principles of clinical governance, informed consent, multidisciplinary care and, ultimately, the legal standard of care.

The medico-legal question is therefore not simply whether aripiprazole lowers prolactin. It is whether introducing a second dopamine-modulating medicine represents a reasonable, proportionate and defensible clinical response in the individual patient.

Off-Label Prescribing and the GMC: Professional Responsibilities

The General Medical Council’s Good practice in prescribing and managing medicines and devices recognises that prescribing outside a medicine’s licence may be appropriate. However, the guidance also makes clear that such prescribing carries enhanced professional responsibilities.

The prescriber should be satisfied that:

• sufficient evidence or clinical experience supports the proposed treatment;
• licensed alternatives have been properly considered;
• the anticipated benefits outweigh foreseeable risks;
• the patient is informed that treatment is being used outside its licensed indication where discussion is practicable;
• material risks and reasonable alternatives are discussed;
• the clinical reasoning is documented; and
• appropriate monitoring arrangements are established.

These obligations become particularly important when the additional medication is not treating the primary psychiatric illness but is instead intended to mitigate an adverse effect of another prescribed psychotropic medicine.

NICE and the Royal College of Psychiatrists: Treat the Whole Patient

NICE guidance on psychosis, schizophrenia and medicines optimisation consistently promotes careful review of antipsychotic adverse effects rather than reflexively adding further medication. Hyperprolactinaemia should prompt reassessment of the overall treatment strategy, consideration of dose reduction where feasible, or switching to a prolactin-sparing antipsychotic if clinically appropriate.

Similarly, the Royal College of Psychiatrists has repeatedly emphasised that in cases of people with severe mental illness experience disproportionate rates of obesity, diabetes, cardiovascular disease, endocrine dysfunction and premature mortality, the College advocates parity of esteem between physical and mental healthcare, requiring psychiatrists to investigate physical illness with the same rigour expected in any other medical specialty.

Persistent hyperprolactinaemia accompanied by type 2 diabetes mellitus, obesity, hypogonadism, osteoporosis or other endocrine abnormalities should therefore trigger consideration of broader endocrine pathology rather than being viewed solely as a medication side effect.

Depot Antipsychotics Create a Higher-Risk Pharmacological Environment

The addition of aripiprazole is particularly complex where the patient remains prescribed depot antipsychotic injections.

Depot preparations cannot be rapidly withdrawn if clinically significant adverse effects develop. Dopamine receptor blockade continues for weeks after administration, substantially reducing therapeutic flexibility.

If adjunctive aripiprazole precipitates akathisia, agitation, insomnia or behavioural deterioration, clinicians cannot immediately remove the underlying pharmacological interaction. Consequently, the threshold for introducing additional dopamine-modulating medication should arguably be higher than in patients treated solely with oral antipsychotics.

Akathisia Is Not a Minor Adverse Effect

Aripiprazole is generally well tolerated, but akathisia remains one of its most clinically significant adverse effects.

Patients frequently describe overwhelming inner restlessness, profound anxiety, inability to remain still, agitation and severe psychological distress. These symptoms can be mistaken for worsening psychosis, anxiety disorders or behavioural disturbance, potentially resulting in further inappropriate prescribing.

The literature has also associated severe untreated akathisia with treatment discontinuation, self-harm and suicidal ideation in some patients.

Where aripiprazole has been prescribed solely to lower prolactin concentrations, the emergence of akathisia fundamentally alters the balance between therapeutic benefit and clinical risk.

Appropriate management should include urgent clinical review, consideration of dose reduction or discontinuation, reassessment of the antipsychotic regimen, symptomatic treatment where indicated, and close follow-up until symptoms resolve.

Multiple Endocrine Abnormalities Should Prompt Endocrinology Referral

The presence of hyperprolactinaemia together with type 2 diabetes mellitus or other endocrine abnormalities should prompt clinicians to ask a broader diagnostic question.

Is the patient experiencing a medication side effect alone, or does the presentation reflect wider endocrine disease requiring specialist investigation?

Potential differential diagnoses include pituitary pathology, hypogonadism, thyroid disease, adrenal disorders, metabolic syndrome and osteoporosis.

Adding aripiprazole may improve one biochemical parameter while delaying diagnosis of another clinically significant disorder.

Referral to a consultant endocrinologist should therefore be strongly considered where endocrine dysfunction extends beyond isolated hyperprolactinaemia, where symptoms remain unexplained, or where long-term complications require specialist assessment.

The Legal Framework: From Bolam to Montgomery

The legal analysis of these prescribing decisions has evolved significantly over recent decades.

Bolam v Friern Hospital Management Committee [1957]

The Bolam principle established that a clinician is not negligent simply because another clinician would have acted differently, provided the decision accords with a responsible body of professional opinion.

Historically, this afforded considerable protection to prescribing decisions supported by accepted clinical practice.

However, modern medical negligence law has moved well beyond Bolam alone.

Bolitho v City and Hackney Health Authority [1998]

The House of Lords refined the Bolam principle by holding that professional opinion itself must withstand logical analysis.

Courts are not obliged to accept expert evidence merely because other clinicians support it. The opinion must demonstrate coherent reasoning and appropriately balance risks against benefits.

In practical terms, this means that merely stating “adjunctive aripiprazole is accepted practice” may be insufficient if inadequate consideration was given to endocrine disease, alternative treatment options, foreseeable adverse effects or the patient’s individual circumstances.

Montgomery v Lanarkshire Health Board [2015]

The Supreme Court fundamentally reshaped informed consent.

Clinicians are now under a legal duty to ensure that patients are informed of:

• material risks associated with proposed treatment;
• reasonable alternative treatment options; and
• the option of declining treatment altogether where appropriate.

A risk is material if a reasonable person in the patient’s position would likely attach significance to it, or if the clinician knows, or should reasonably know that the particular patient would likely consider it significant.

Applied to adjunctive aripiprazole, this means patients should ordinarily be informed about:

• the off-label nature of treatment;
• the possibility of akathisia, agitation and insomnia;
• the possibility that treatment may not adequately resolve symptoms;
• alternatives such as dose reduction, switching antipsychotics where clinically feasible, observation, or referral for endocrine assessment;
• the uncertainties associated with adding another psychotropic medicine.

Failure to discuss these matters may expose clinicians to criticism even where prescribing itself was pharmacologically reasonable.

Documentation: The Clinician’s Strongest Defence

In medico-legal practice, contemporaneous documentation frequently determines whether a prescribing decision can be defended.

The medical record should clearly demonstrate:

• why adjunctive aripiprazole was preferred over alternative strategies;
• evidence supporting off-label prescribing;
• informed consent discussions;
• endocrine and metabolic assessment;
• monitoring plans;
• review arrangements;
• contingency planning should adverse effects emerge.

Documentation should reflect a process of clinical reasoning rather than simply recording a prescribing decision.

Conclusion

Adjunctive aripiprazole remains a legitimate therapeutic option for selected patients with antipsychotic-induced hyperprolactinaemia. However, legitimacy does not eliminate professional responsibility.

Current GMC guidance, NICE recommendations and Royal College of Psychiatrists policy all point towards careful assessment, shared decision-making, systematic physical health monitoring and multidisciplinary management.

The legal authorities of Bolam, Bolitho and Montgomery reinforce these professional duties by requiring that prescribing decisions are supported by logical clinical reasoning, informed by responsible practice, and accompanied by meaningful patient involvement.

Where a patient receiving depot antipsychotic treatment develops persistent hyperprolactinaemia alongside diabetes mellitus or other endocrine abnormalities, the question should not simply be how to suppress prolactin. The more important question is whether the patient requires comprehensive endocrine investigation before additional psychotropic medication is introduced.

In many such cases, early referral to a consultant endocrinologist, combined with a multidisciplinary review of the antipsychotic regimen, is likely to represent the most clinically robust and the most legally defensible course of action.